Methotrexate in juvenile idiopathic arthritis. Adverse effects and associated factors

Abstract

Methotrexate (MTX) is the drug of choice for juvenile idiopathic arthritis. Its clinical efficacy is limited due to the development of adverse effects (AEs). A retrospective observational study was conducted on the AEs associated with MTX therapy in children diagnosed with juvenile idiopathic arthritis followed-up in a tertiary hospital between 2008 and 2016. The study included a total of 107 patients, of whom 71 (66.3%) were girls (66.3%). The median age at diagnosis was 6.4 years (IQR 3.1-12.4), with a median follow-up of 45.7 months (IQR 28.8-92.4). There were 48 patients (44.9%) with oligoarthritis, and 26 children (24.3%) with rheumatoid-factor negative polyarthritis. Of these, 52/107 (48.6%) developed AEs, with the most frequent being gastrointestinal symptoms (35.6%) and behavioural problems (35.6%). An age older than 6 years at the beginning of therapy increased the risk of developing AEs, both in the univariate (OR=3.5; 95% CI: 1.5-7.3) and multivariate (12% increase per year) analyses. The doses used, administration route, or International League of Associations for Rheumatology (ILAR) classification, were not associated with the development of AEs. Twenty children required a dosage or route of administration modification, which resolved the AE in 11 (55%) cases. MTX was interrupted due to the development of AEs in 37/107 patients (34.6%), mainly due to increased plasma transaminases (n=14, 37.8%), gastrointestinal symptoms (n=9, 24.3%) and behavioural problems (n=6, 16.3%). MTX is the therapy of choice for patients with juvenile idiopathic arthritis, but 50% of the children develop some form of AE. Although the AEs are not severe, they lead to interruption of therapy in 35% of the children.